Cathepsin L is significantly associated with apoptosis and plaque destabilization in human atherosclerosis
Cathepsin L is significantly associated with apoptosis and plaque destabilization in human atherosclerosis
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DOI：
10.1016/j.atherosclerosis.2008.03.027
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发表时间：
2009-01-01
期刊：
影响因子：
5.3
通讯作者：
Yuan, Xi-Ming
中科院分区：
文献类型：
--
作者：
Li, Wei;Kornmark, Louise;Yuan, Xi-Ming
目的：人类动脉粥样硬化病变过度表达弹性蛋白溶解和胶原溶解组织蛋白酶，但其病理意义尚不清楚。本研究的目的是探讨组织蛋白酶L的表达与乳腺癌的关系。巨噬细胞凋亡在冠状动脉疾病（CAD）患者、临床症状和斑块的严重程度人颈动脉粥样硬化.方法和结果：人颈动脉粥样硬化病变（n = 49）的定量免疫组织化学分析显示，溶酶体组织蛋白酶L的表达在具有坏死核心形成和冠状动脉破裂的动脉粥样硬化斑块中显著增加。在这些斑块中，组织蛋白酶L主要与CD 68阳性巨噬细胞相关，而检测到平滑肌细胞肌动蛋白水平显著降低。这些斑块中组织蛋白酶L的表达也与细胞凋亡和应激蛋白铁蛋白相关。有症状患者的斑块中组织蛋白酶L水平较无症状患者显著升高。来自CAD患者（n = 7）的人单核细胞衍生的巨噬细胞显示出与来自匹配的健康供体（n = 7）的细胞相比显著更高水平的组织蛋白酶L、细胞脂质和细胞凋亡。7 β-羟基胆固醇显著增强了健康供体细胞中的组织蛋白酶L，但在CAD患者细胞中没有。而且。结论：组织蛋白酶L参与了巨噬细胞的死亡、坏死核心的形成和动脉粥样硬化斑块的不稳定性。巨噬细胞溶酶体组织蛋白酶L和相关的凋亡可能是人类动脉粥样硬化易损斑块调制或成像的潜在靶点。(C)2008爱思唯尔爱尔兰有限公司保留所有权利。
Objective: Human atherosclerotic lesions overexpress elastolytic and collagenolytic cathepsins with unclear pathological implications. The aim of this study was to investigate the relationship among expression of cathepsin L. macrophage apoptosis in coronary artery disease (CAD) patients, clinical symptoms and plaque severity Of human carotid atheroma.Methods and results: Quantitative immunohistochemical analysis of human carotid atherosclerotic lesions (n = 49) showed that expression of lysosomal cathepsin L was significantly increased in atherosclerotic plaques with formation of the necrotic core and rupture of the cap. In those Plaques, cathepsin L was associated mainly with CD68-positive macrophages, whereas significant lower levels of smooth muscle cell actin were detected. The expression of cathepsin L in these plaques was also correlated with apoptosis and the stress protein ferritin. Plaques from symptomatic patients showed greater increased levels of cathepsin L than those front asymptomatic patients. Human monocyte-derived macrophages from CAD patients (n = 7) showed significantly higher levels of cathepsin L, cellular lipids and apoptosis versus cells from matched healthy donors (n = 7). 7Beta-hydroxycholesterol significantly enhanced cathepsin L in cells from healthy donors but not in Cells from CAD patients. Moreover. macrophage apoptosis was significantly correlated with expression of cathepsin L in cell nuclei and membranes.Conclusion: The results Suggest that cathepsin L is involved in death of macrophages necrotic Core formation and development of atherosclerotic plaque instability. Macrophage lysosomal cathepsin L and related apoptosis may be potential targets for modulation or imaging of vulnerable plaques in human atherosclerosis. (C) 2008 Elsevier Ireland Ltd. All rights reserved.